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Biological Activity:

CB-5083 is a highly potent, selective and orally bioavailable p97 AAA ATPase inhibitor with IC50 ~11 nM. Treatment of tumor cells with CB-5083 leads to accumulation of poly-ubiquitinated proteins, retention of endoplasmic reticulum-associated degradation (ERAD) substrates, and generation of irresolvable proteotoxic stress, leading to activation of the apoptotic arm of the unfolded protein response. In xenograft models, CB-5083 causes modulation of key p97-related pathways, induces apoptosis, and has antitumor activity in a broad range of both hematological and solid tumor models.

How to Use:

In vitro: CB-5083 was used at 1-2.5 μM final concentration in various assays.
In vivo: CB-5083 was dosed to mice orally at 25-100 mg/Kg once or twice per day.

Reference:

• 1. Zhou HJ, et al. Discovery of a First-in-Class, Potent, Selective, and Orally Bioavailable Inhibitor of the p97 AAA ATPase (CB-5083). (2015) J Med Chem. 58(24):9480-97.?
• 2. Anderson DJ, et al. Targeting the AAA ATPase p97 as an Approach to Treat Cancer through Disruption of Protein Homeostasis. (2015) Cancer Cell. 28(5):653-65.?